Pathophysiology of prion accumulation in skeletal muscle
Final Report Abstract
With the help of this grant, we were able to further investigate the pathophysiology of PrPSc accumulation in skeletal muscle following experimental prion infection. Using primate and rodent animal models we showed that: - Propagation of PrPSc in clinical but also preclinical disease states is prion strain dependant, - PrPSc preferentially propagates in highly innervated muscle, - Presence of PrPSc within muscle is inhomogeneous, - Myositis positively influences PrPSc propagation in muscle, - Propagation of PrPSc in myositis-muscle depends on PrPC expressing hematopoietic compartment, - Muscle is not able to sustain PrPSc accumulation in early disease states in the absence of myositis. These results contribute to widen our understanding on the pathophysiology of prion diseases especially on the peripheral pathogenesis. Furthermore, they are valuable in guiding decisions regarding the use of muscle biopsy as a diagnostic test to establish the diagnosis of a human prion disease.
Publications
- Preclinical deposition of pathological prion protein in muscle of experimentally infected primates. PLoS One. 2010 Nov 11;5(11):e13906
Krasemann S, Neumann M, Geissen M, Bodemer W, Kaup FJ, Schulz-Schaeffer W, Morel N, Aguzzi A, Glatzel M
